The candidate is a clinical and biological psychologist who seeks to acquire the skills in conducting clinical trials outcome research for nicotine, alcohol, and other drug dependencies. This award will allow the candidate to advance science-based treatment into clinical practice, by providing training, mentorship, and experience in relevant methodologies to combine pharmacotherapy and psychosocial treatment. The candidate will also expand her previous laboratory research background to study subjective, behavioral, and physiological factors involved in alcohol and drug reinforcement and their relation to clinical outcome. Throughout the award, Dr. King will engage in course work, workshops, laboratory and pilot clinical trial research, and have ongoing mentorship from experts in the field. Concurrent heavy use of alcohol and tobacco is common. However, the mechanisms of combined reinforcement and the optimal treatment strategies for heavy users of both drugs have not been delineated. The proposed study will examine the effects of combining naltrexone with standard smoking cessation treatment in heavy smokers with moderate-to-heavy drinking patterns. The rationale for this study derives from the candidate's recent preliminary data. These data indicate that naltrexone significantly reduced heavy smokers' craving for cigarettes after smoking one cigarette and a subsequent one hour rest period. Also in heavy smokers, naltrexone decreased the number of choice cigarettes smoked, lowered carbon monoxide (CO) levels, and acutely increased cortisol response to the first cigarette compared to placebo, suggesting a potential mechanism of reduced craving. We hypothesize that naltrexone will be particularly efficacious as an adjunctive treatment in moderate-to-heavy drinking smokers, an historically treatment refractory subgroup. Naltrexone might directly reduce craving or number of cigarettes smoked, or decrease alcohol intake and indirectly reduce cigarette smoking, since studies have shown that alcohol drinking enhances subsequent urge to smoke. Consumption patterns and quit rates for both substances will be monitored throughout the study. We will also investigate the relationship between response to naltrexone in the laboratory to response in a clinical trial, which will enable us to explore potential mechanisms for heightened response to opioid antagonists. Examining a targeted treatment combining pharmacotherapy and behavioral treatment for this subgroup is of great importance, as alcohol abusers show increased mortality more due to tobacco than alcohol-related illness.